April 8, 2017 – A guiding principle of developmental biology is the fact that differential gene expression determines the distinctive properties of each cell type. Lineage-specific transcription factors are required for these cell lineages. In the case of hematopoiesis, the GATA1-ES cells contribute to many cell types and organs but not erythroid cells — lineage-restricted transcription factors determine hematopoietic cell fate. To better understand the genomics of hematopoiesis, Dr. Hardison and colleagues have embarked on a projected named VISION.
The rationale of the VISION project is that acquiring genome-wide epigenetic data across various stages in hematopoiesis is no longer a barrier to the understanding of the mechanism of gene regulation during normal or pathological tissue development. The chief challenges remain in integrating epigenetic data in terms that are accessible and understandable to a broad community of researchers. As part of VISION, Dr. Hardison and his colleagues want to build and validate quantitative models explaining how the dynamics of gene expression relates to epigenetic features, and translate information effectively from mouse models to potential application in human health.
As part of the VISION project, they also developed sensitive and robust methods to reveal regulatory landscapes in rare cells and study gene expression and chromatin states across hematopoiesis. Their model is based on studying the action of key transcription factors that drive gene expression pattern and determine cell types. They have studied erythroid differentiation in cultured and primary cells and captured the transcriptional response to GATA1-ER activation in G1E cells. They have found transcription factors regulate lineage-specific genes, and context differs between induce and repressed genes. These contexts can be due to the sequence motifs or conservation patterns. They also assayed genome-wide epigenetic features associated with transcriptional regulation and found TAL1 and GATA1 occupancy to govern induction. They identified distinct cohorts of transcription factors regulating genes during differentiation.
The project is indeed very interesting. With advancing high throughput technologies the challenge is truly no longer in getting data. It is in fact in making sense of whatever we have now. The VISION project is a step in that direction, where they aim to combine existing epigenomic data, try to integrate them to derive quantitative rules that can be applied globally.